Investigation of patients with Neurological Dysfunction. The general aim of this project is to obtain more precise understanding of multiple factors possibly related either singly or in combination to the pathogenesis of a number of neurological disorders including multiple sclerosis, myasthenia gravis, polyneuropathy and other neuromuscular diseases. The studies of multiple sclerosis include a detailed evaluation of the histocompatibility makeup and the relationship between immunogenetic background and clinical disease as well as immunological function including the cellular response to various human viruses. Nuclear magnetic resonance imaging is being used to assess the extent and magnitude of lesions in the white matter. These studies are performed in patients with sporadic disease, patients with a family history of demyelinating disease as well as identical and nonidentical twins who are either concordant or discordant for MS. Cerebrospinal fluid immunoglobulin content and specificity are being evaluated by new highly sensitive techniques. Trials of experimental therapeutic approaches are being conducted in carefully selected patients with multiple sclerosis. One trial currently in progress involves the administration of Poly ICLC an interferon inducer. Studies of myasthenia gravis are directed at assessment of lymphocyte markers in the blood and thymus. The reactivity of thymocytes and blood lymphocytes to acetylcholine receptor is being evaluated and correlated with antibodies to acetylcholine receptor in the blood. In myasthenia gravis and a wide range of other neuromuscular disorders, detailed electrophysiological evaluation, histopathological studies of muscle and nerve are being conducted.